JPH02215772A - Production of imidazole derivative - Google Patents
Production of imidazole derivativeInfo
- Publication number
- JPH02215772A JPH02215772A JP1037106A JP3710689A JPH02215772A JP H02215772 A JPH02215772 A JP H02215772A JP 1037106 A JP1037106 A JP 1037106A JP 3710689 A JP3710689 A JP 3710689A JP H02215772 A JPH02215772 A JP H02215772A
- Authority
- JP
- Japan
- Prior art keywords
- imidazole derivative
- formula
- group
- methanol
- organic solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000002460 imidazoles Chemical class 0.000 title abstract description 10
- 238000004519 manufacturing process Methods 0.000 title description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 3
- 125000003118 aryl group Chemical group 0.000 claims abstract description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 3
- 239000012279 sodium borohydride Substances 0.000 claims description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 abstract description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 239000002904 solvent Substances 0.000 abstract description 4
- 239000003905 agrochemical Substances 0.000 abstract description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract description 2
- 150000005690 diesters Chemical group 0.000 abstract description 2
- 150000003385 sodium Chemical class 0.000 abstract 2
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical class [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 abstract 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000009835 boiling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- -1 methyl 1-triphenylmethyl-4-hydroxymethyl-IH-imidazole-5-carboxylate Chemical compound 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、医薬及び農薬の中間体として有用なモノメチ
ロール基を有するイミダゾール誘導体の新規な製造方法
に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a novel method for producing imidazole derivatives having a monomethylol group that are useful as intermediates for pharmaceuticals and agricultural chemicals.
（従来の技術）
モノメチロール基を有するイミダゾール誘導体の製造法
についてはジエステル基を有するイミダゾール誘導体を
水素化ホウ素リチウムによるか又は水素化ホウ素ナトリ
ウムと臭化リチウムの混合物による還元にて得られてい
た。(Prior Art) As for a method for producing an imidazole derivative having a monomethylol group, an imidazole derivative having a diester group was obtained by reduction with lithium borohydride or a mixture of sodium borohydride and lithium bromide.
（Ｊ 、Ｌａｂｅｌｌｅｄ Ｃｏｍｐｏｕｎｄｓ ａｎ
ｄ ＲａｄｉｏｐｈａｒＩＩｌａｃｅｕｔｉｃａｌｓ
ｖｏｌ ＸＸ１１１（Ｎｏｔ）３５（１９８５）及びＣ
ａｎ、 Ｊ 、 ＣｈｅＩＩ＋しかし、この方法では反
応に長時間を要し、かつ低収率であり、又還元剤が高価
であるという工業上不利な点があった。(J, Labeled Compounds and
dRadiophar II Laceuticals
vol XX111 (Not) 35 (1985) and C
an, J, CheII+ However, this method has industrial disadvantages in that the reaction takes a long time, the yield is low, and the reducing agent is expensive.
本発明の目的は農医薬の中間体として有用なモノメチロ
ール基を存するイミダゾール誘導体を実用的に収率良く
、簡単に製造出来る方法を提供する事である。An object of the present invention is to provide a method for easily producing imidazole derivatives containing a monomethylol group, which are useful as intermediates for agricultural and pharmaceutical products, with good practical yield.
本発明者らは、種々の検討を行なった結果、本発明に到
達した。すなわち本発明は一般式（Ｔ）晶・
（式中Ｒはアルキル基、アラルキル基又はアリール基、
Ｒ′’はベンジル基又はトリフェニルメチル基を示す、
）で表される化合物と、水素化ホウ素ナトリウムとを有
機溶媒中メタノールの存在下で反応させる事を特徴とす
る一般式（Ｉｔ）滴下する事により進行させる事が出来
る０反応は４０℃から用いる溶媒の沸点までの温度で、
メタノール滴下後更に３０分から数時間行なう、有機溶
媒としてはクロロホルム等のハロゲン化炭化水素類、Ｔ
ＨＦ等のエーテル類、トルエン等の炭化水素類が使用出
来る。水素化ホウ素ナトリウムはイミダゾール誘導体に
対してｌ−１０倍モル、好ましくは４〜５倍モルを使用
する事が望ましい。The present inventors have arrived at the present invention as a result of various studies. That is, the present invention is a crystal of the general formula (T) (wherein R is an alkyl group, an aralkyl group, or an aryl group,
R'' represents a benzyl group or a triphenylmethyl group,
) is reacted with sodium borohydride in the presence of methanol in an organic solvent.The general formula (It) is characterized by reacting the compound represented by () with sodium borohydride in the presence of methanol. At a temperature up to the boiling point of the solvent,
After dropping methanol, the process is continued for another 30 minutes to several hours.As an organic solvent, halogenated hydrocarbons such as chloroform, T
Ethers such as HF and hydrocarbons such as toluene can be used. It is desirable to use sodium borohydride in an amount of 1-10 times, preferably 4 to 5 times, the amount of the imidazole derivative.
次に実施例を挙げ、本発明を更に詳細に説明する。 Next, the present invention will be explained in more detail with reference to Examples.
実施例１
＾・
（式中Ｒ及びＲ′は前項と同一内容を示す、）で表され
る化合物の製造法である０反応は有機溶媒中、水素化ホ
ウ素ナトリウムと一般式〔１］で表されるジエステル基
を有するイミダゾール誘導体との混合物に所定の温度に
於いてメタノールをジメチル １−トリフェニルメチル
−ＩＨ−イミダゾール−４，５−ジカルボキシレ−１−
１９，５ｇをクロロホルム１８０ｍに懸濁させた０次い
で室温で水素化ホウ素ナトリウム８．８ｇを添加した。Example 1 The 0 reaction, which is a method for producing a compound represented by ^- (in the formula, R and R' have the same content as in the previous section), is a reaction represented by the general formula [1] with sodium borohydride in an organic solvent. Dimethyl 1-triphenylmethyl-IH-imidazole-4,5-dicarboxylene-1-
Then, 8.8 g of sodium borohydride was added at room temperature.
加熱して還流させた後メタノール３７Ｍ１を１時間要し
て滴下した。還流下更に５時間攪拌した０反応液を氷水
１．８１に注ぎ、次いで分液後有機層を飽和食塩水で洗
浄し、硫酸マグネシウムで乾燥後溶媒を留去した。残分
に８０％メタノール５０１１を加え撹拌後ろ過し、乾燥
してメチル １−トリフェニルメチル−４−ヒドロキシ
メチル−ＩＨ−イミダゾール−５−カルボキシレート１
４．８ ｇを得た。収率８１．４％、沸点１５９−１６
１°Ｃ実施例２
反応溶媒をクロロホルムからＴＨＦに変えた以外は実施
例１と同様な仕込比で反応を行なった。After heating and refluxing, 37M1 of methanol was added dropwise over 1 hour. The reaction mixture was stirred under reflux for an additional 5 hours, and then poured into 1.81 g of ice water. After separation, the organic layer was washed with saturated brine, dried over magnesium sulfate, and the solvent was distilled off. 80% methanol 5011 was added to the residue, stirred, filtered, and dried to give methyl 1-triphenylmethyl-4-hydroxymethyl-IH-imidazole-5-carboxylate 1.
4.8 g was obtained. Yield 81.4%, boiling point 159-16
1°C Example 2 The reaction was carried out at the same charging ratio as in Example 1 except that the reaction solvent was changed from chloroform to THF.
メタノール滴下終了後３０分で氷水１．８１に注ぎ撹拌
後ろ過した。水洗後結晶をクロロホルムに溶解し、水、
飽和食塩水で洗浄後硫酸マグネシウムで乾燥した。溶媒
留去後、実施例１と同様な処理を行ないメチル １−ト
リフェニルメチル−４−ヒドロキシメチル−ＩＨ−イミ
ダゾール−５−カルボキシレート１３．８ ｇを得た。Thirty minutes after the completion of the methanol dropwise addition, the mixture was poured into 1.8 g of ice water, stirred, and filtered. After washing with water, dissolve the crystals in chloroform, water,
After washing with saturated brine, it was dried over magnesium sulfate. After distilling off the solvent, the same treatment as in Example 1 was performed to obtain 13.8 g of methyl 1-triphenylmethyl-4-hydroxymethyl-IH-imidazole-5-carboxylate.
収率７５．７％〔発明の効果〕
本発明の製造方法は、医薬及び農薬の中間体として重要
な一般式〔■〕で表わされるイミダゾール誘導体を安価
な水素化ホウ素ナトリウムを使用し、しかも高収率で得
られるので、工業的に優れた製造方法である。Yield: 75.7% [Effects of the Invention] The production method of the present invention uses inexpensive sodium borohydride to produce an imidazole derivative represented by the general formula [■], which is important as an intermediate for pharmaceuticals and agricultural chemicals. Since it can be obtained in high yield, it is an industrially excellent manufacturing method.
Claims (1)
Ｒ′はベジル基又はトリフェニルメチル基を示す。）で
表される化合物と水素化ホウ素ナトリウムとを有機溶媒
中、メタノールの存在下で反応させる事を特徴とする一
般式 ▲数式、化学式、表等があります▼ （式中Ｒ及びＲ′は前記と同じ意味を有す。）で表され
る化合物の製造方法。(1) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R alkyl group, aralkyl group or aryl group,
R' represents a bezyl group or a triphenylmethyl group. ) and sodium borohydride in an organic solvent in the presence of methanol ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R and R' are the has the same meaning as ).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1037106A JPH02215772A (en) | 1989-02-16 | 1989-02-16 | Production of imidazole derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1037106A JPH02215772A (en) | 1989-02-16 | 1989-02-16 | Production of imidazole derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH02215772A true JPH02215772A (en) | 1990-08-28 |
Family
ID=12488344
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1037106A Pending JPH02215772A (en) | 1989-02-16 | 1989-02-16 | Production of imidazole derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02215772A (en) |
-
1989
- 1989-02-16 JP JP1037106A patent/JPH02215772A/en active Pending
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